title: Long-lasting molecular changes in human skin after repetitive in situ UV irradiation.
abstract: It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at > or = 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at > or = 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.
authors.affiliation: Department of Dermatology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Brenner
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Coelho
authors.forename: Janusz Z
authors.initials: JZ
authors.lastname: Beer
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Miller
authors.forename: Rainer
authors.initials: R
authors.lastname: Wolber
authors.forename: Christoph
authors.initials: C
authors.lastname: Smuda
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules / Q000032:analysis; D018925:Chemokines; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008543:Melanins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D044023:Receptor, Endothelin B / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects*; D012880:Skin Pigmentation / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018925:Chemokines; C501126:DKK1 protein, human; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D044023:Receptor, Endothelin B; D017978:Receptors, Growth Factor